Patients with rapid cycling bipolar disorder experience at least four episodes of affective illness (depression, hypomania, and/or mania) in a year and are frequently resistant to conventional treatments. Therefore, this psychiatric illness warrants further study because of its significant morbidity. In addition, since rapid cycling patients experience frequent mood shifts that are accompanied by dramatic changes in the sleep-wake cycle, they present a promising opportunity to study the relationships between sleep activity, and mood disorders. This project studies the circadian rhythms of rapid cycling patients and is the first in a series of planned studies designed to elucidate the etiology of rapid cycling bipolar disorder and to test several experimental treatments. In the current study, rapid cycling patients record their mood and sleep on a daily basis over an extended period of time. In addition, since the majority of rapid cycling patients are premenopausal women, we are particularly interested in the relationship between the menstrual cycle and the affective state of rapid cycling women. Each month, female subjects record their menstrual cycles and monitor their urine for the ovulatory LH surge. All patients, both male and female, intermittently wear temperature and activity monitors on an outpatient basis. Patients are admitted to the hospital for brief, intensive chronobiological evaluations twice in the course of the study: once shortly after they switch into the hypomanic state, and once shortly after they switch into the depressive state. The hospitalizations are each 48 hours in duration and consist of a 20-hour "naturalistic day" and a 28-hour constant routine. The constant routine is designed to minimize the effects of light, sleep, activity, and caloric loading on the patient's circadian rhythms. During the hospitalizations, patients wear rectal temperature probes and activity monitors, and blood is withdrawn every twenty minutes through an indwelling intravenous catheter. By analyzing temperature data and by measuring the secretion of melatonin, cortisol, and other hormones, we will have extensive information about the circadian rhythms of rapid cycling bipolar patients, and about how those rhythms differ in the depressed and hypomanic states. Because the project is in its early stages, results are not available at this time. Other projects on the pathophysiology and treatment of rapid cycling are currently being planned. These include trials of L-thyroxine and bright light in the treatment of rapid cycling, and a protocol using Leuprolide acetate, a GnRH agonist, to explore the role of gonadal steroids in rapid cycling in women.